Weight loss, fatigue, and renal failure
TREATMENT OF RENAL SARCOIDOSIS
6. Which is a first-line therapy for renal sarcoidosis?
- Corticosteroids
- Azathioprine
- Mycophenolate mofetil
- Infliximab
- Adalimumab
Treatment of impaired calcium homeostasis in sarcoidosis includes hydration; reducing intake of calcium, vitamin D, and oxalate; and limiting sun exposure.11,31 For more significant hypercalcemia (eg, serum calcium levels > 11 mg/dL) or nephrolithiasis, corticosteroid therapy is the first choice and should be implemented at the first sign of renal involvement. Corticosteroids inhibit the activity of 1-alpha-hydroxylase in macrophages, thereby reducing the production of 1,25-dihydroxyvitamin D.
Chloroquine and hydroxychloroquine have been mentioned in the literature as alternatives to corticosteroids.32 But the effect of these agents is less predictable and is slower than treatment with corticosteroids. Ketoconazole has no effect on granuloma formation but corrects hypercalcemia by inhibiting calcitriol production, and can be used as an adjunct for treating hypercalcemia and hypercalciuria.
Corticosteroids are the mainstay of treatment for renal sarcoidosis, including granulomatous interstitial nephritis and interstitial nephritis without granulomas. Most patients experience significant improvement in renal function. However, full recovery is rare, likely as a result of long-standing disease with some degree of already established irreversible renal injury.16
Corticosteroid dosage
There is no standard dosing protocol, but patients with impaired renal function due to biopsy-proven renal sarcoidosis should receive prednisone 0.5 to 1 mg/kg/day, depending on the severity of the disease, in a single dose every morning.
The optimal dosing and duration of maintenance therapy are unknown. Based on studies to date, the initial dosing should be maintained for 4 weeks, after which it can be tapered by 5 mg each week down to a maintenance dosage of 5 to 10 mg/day.4
Patients with a poor response after 4 weeks tend to have a worse renal outcome and are more susceptible to relapse.15 Fortunately, relapse often responds to increased corticosteroid doses.11,15 In the case of relapse, the dose should be increased to the lowest effective dose and continued for 4 weeks, then tapered more gradually.
A total of 24 months of treatment seems necessary to be effective and to prevent relapse.15 Some authors have proposed a lifelong maintenance dose for patients with frequent relapses, and some propose it for all patients.4
Other agents
Tumor necrosis factor (TNF)-blocking agents. Considering the critical role TNF plays in granuloma formation, anti-TNF-alpha agents are useful in steroid-resistant sarcoidosis.33 A thorough workup is necessary before starting these agents because of the increased risk of serious infection, including reactivation of latent tuberculosis. Of the current TNF-blocking agents, infliximab is most often used in renal sarcoidosis.34 Experience with adalimumab is more limited, though promising results indicate it could be an alternative for patients who do not tolerate infliximab.35
Azathioprine, mycophenolate mofetil, or methotrexate may also be used as a second-line agent if treatment with corticosteroids is not tolerated or does not control the disease. The evidence in support of these agents is limited. In small series, they have allowed sustainable control of renal function while reducing the steroid dose. Currently, these agents are used for patients resistant to corticosteroid therapy, who would otherwise need prolonged high-dose corticosteroid treatment, or who have corticosteroid intolerance; they allow a more effective steroid taper and maintenance of stable renal function.15,36
The data supporting a standardized treatment of renal sarcoidosis are limited. For steroid intolerance or resistance, cytotoxic drugs and selected anti-TNF-alpha agents, as mentioned above, have shown promise in improving or stabilizing serum creatinine levels. Further exploration is required as to which agent or combination is better at limiting the disease process with fewer adverse effects.
Our patient was initially treated with corticosteroids and was ultimately weaned to a maintenance dose of 5 mg/day. He was followed as an outpatient and was started on mycophenolate mofetil in place of higher steroid doses. His renal function stabilized, but he was lost to follow-up after 2 years.
KEY POINTS
- Sarcoidosis is a multisystem granulomatous disease that most commonly involves the lungs, skin, and reticuloendothelial system.
- Renal involvement in sarcoidosis is likely underestimated due to its often clinically silent nature and the possibility of missing typical granulomatous lesions in a small or less-than-optimal biopsy sample.
- Manifestations of renal sarcoidosis include disrupted calcium homeostasis, nephrocalcinosis, nephrolithiasis, and renal failure.
- Because the clinical and histopathologic manifestations of renal sarcoidosis are nonspecific, the diagnosis is one of exclusion. In patients with renal failure or with hypercalcemia or hypercalciuria of unknown cause, renal sarcoidosis should be included in the differential diagnosis. Patients with chronic sarcoidosis should also be screened for renal impairment.
- Granulomatous interstitial nephritis is the classic histologic finding of renal sarcoidosis. Nonetheless, up to one-third of patients have interstitial nephritis without granulomas.
- Corticosteroids are the mainstay of treatment for renal sarcoidosis. An initial dose of oral prednisone 0.5 to 1 mg/kg/day should be maintained for 4 weeks and then gradually tapered to 5 to 10 mg/day for a total of 24 months. Some patients require lifelong therapy.
- Several immunosuppressive and cytotoxic agents may be used in cases of corticosteroid intolerance or to aid in effective taper of corticosteroids.
